Microtome waste removal assembly

ABSTRACT

A sample sectioning device including a housing having a base member, a cutting mechanism positioned on the base member and operable to cut sections from a sample, a sample holder dimensioned to hold a sample and operable to move with respect to the cutting mechanism during a cutting operation, and a waste removal assembly positioned below the cutting mechanism and the sample holder, the waste removal assembly having a first member and a second member that are dimensioned to remove waste produced during the cutting operation.

CROSS-REFERENCE TO RELATED APPLICATION

The application is a non-provisional application of co-pending U.S.Provisional Application No. 62/421,755, filed Nov. 14, 2016 andincorporated herein by reference.

BACKGROUND Field

Embodiments of the invention relate to microtomes or other tissue samplesectioning devices to produce sections of samples, specifically, someembodiments relate to microtomes or other tissue sample sectioningdevices that have a light source, a generator, built in accessorystorage, accessory tray, paraffin removal assembly and/or alarm.

Background Information

Histology is a science or discipline associated with the preparation oftissue specimens for examination or analysis. The examination oranalysis may be of the cellular level, chemical composition, tissuemorphology or composition, or other tissue characteristics.

In histology, a sample of tissue may be prepared for sectioning by amicrotome or other sample sectioning device. Commonly, the tissue may bedried or dehydrated by removing most or almost all of the water from thetissue, for example by exposing the tissue to one or more dehydratingagents. After dehydrating the tissue, clearing of the dehydrating agentsmay be performed, and then an embedding agent (e.g., wax with addedplasticizers) may be introduced or infiltrated into the dehydratedtissue. The removal of the water and the infiltration of the embeddingagent may preserve the tissue specimen for ten (10) and more years andmay aid in sectioning the tissue into thin sections using a microtome.

Embedding may then be performed on the tissue. During embedding, thetissue that has been dehydrated and infiltrated with the embedding agentmay be embedded into a block using one of various waxes, or variouspolymers, or another embedding medium. Representatively, the dehydratedand wax-infiltrated tissue may be placed in a mold and/or cassette,melted wax may be dispensed over the tissue until the mold has beenfilled with the wax, and then the wax may be cooled and hardened.Embedding the tissue into a block of wax may help to provide additionalsupport during cutting or sectioning of the tissue specimen with amicrotome.

The microtome may be used to cut thin slices or sections of the sampleof tissue. Various different types of microtomes are known in the arts.Representative types include, for example, sled, rotary, vibrating, saw,and laser microtomes. The microtomes may be manual or automated.Automated microtomes may include motorized systems or drive systems todrive or automate a cutting movement between the sample from which thesections are to be cut and a cutting mechanism used to cut the sections.Manual microtomes may rely upon rotation of a hand wheel to drive thecutting movement. It is to be appreciated that microtomes may also beused for other purposes besides just histology, and that microtomes maybe used on other types of samples besides just embedded tissue.

SUMMARY

In some embodiments, the invention is directed to a sample sectioningdevice including a housing having a base member, a cutting mechanismpositioned on the base member and operable to cut sections from asample, a sample holder dimensioned to hold a sample and operable tomove with respect to the cutting mechanism during a cutting operation,and a waste removal assembly positioned below the cutting mechanism andthe sample holder, the waste removal assembly having a first member anda second member that are dimensioned to remove waste produced during thecutting operation. In some cases, the first member and the second memberare each movably connected to the base member and operable to movebetween a first position in which they are at a first angle with respectto the base member and a second position in which they are at a secondangle with respect to the base member, wherein the second angle isgreater than the first angle. In some cases, the first member and thesecond member are operable to move with respect to the base memberbetween a first angle of incline and a second angle of incline, whereinthe second angle of incline is approximately 90 degrees and is greaterthan the first angle of incline. The cutting mechanism may be operableto slide with respect to the base member, and sliding of the cuttingmechanism may cause the first member and the second member to move withrespect to one another. The first member and the second member may forma pitched surface below the cutting mechanism and the sample holder. Thefirst member and the second member may be fixed with respect to oneanother. The device may further include a temperature controlling membercoupled to the first member or the second member to control atemperature thereof.

In other embodiments, the invention is directed to a waste removalassembly for a sample sectioning device including a first inclinedmember coupled to a microtome housing, a second inclined member coupledto a microtome housing, and an actuator movably coupled to the firstinclined member and the second inclined member, and the actuator isoperable to cause a slope of one of the first inclined member or thesecond inclined member to change. The first inclined member and thesecond inclined member may be metal plates. One of the first inclinedmember or the second inclined member may include a plate having an edgethat is coupled to the sample sectioning device by a hinge. The slope ofthe first inclined member or the second inclined member may be a firstslope, and the actuator may cause the first inclined member or thesecond inclined member to change to a second slope, and the second slopemay be greater than the first slope. The actuator may cause the slope ofone of the first inclined member or the second inclined member to changewithin a range of ninety degrees with respect to horizontal. Theactuator may be a cutting mechanism of the sample sectioning device, anda sliding of the cutting mechanism causes the slope of one of the firstinclined member or the second inclined member to change. In some cases,the actuator may include an actuating member and a protrusion, and theactuating member slides the protrusion under the first inclined memberand the second inclined member to change the slope. The actuator may bemanually operated by a user. The actuator may be automated. In somecases, a thermoelectric cooler (TEC) may be coupled to the first memberor the second member to control a temperature thereof.

The above summary does not include an exhaustive list of all aspects ofthe present invention. It is contemplated that the invention includesall apparatuses that can be practiced from all suitable combinations ofthe various aspects summarized above, as well as those disclosed in theDetailed Description below and particularly pointed out in the claimsfiled with the application. Such combinations have particular advantagesnot specifically recited in the above summary.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The invention may best be understood by referring to the followingdescription and accompanying drawings that are used to illustrateembodiments of the invention. In the drawings:

FIG. 1 illustrates a schematic view of an embodiment of a microtome orother sample sectioning device.

FIG. 2 illustrates one embodiment of a perspective view of a sampleholder.

FIG. 3A illustrates another perspective view of the sample holder ofFIG. 2.

FIG. 3B illustrates a cross-sectional side view of the sample holder ofFIG. 3A.

FIG. 4 illustrates a back side perspective view of the sample holder ofFIG. 2.

FIG. 5 illustrates a cross-sectional bottom perspective view of thesample holder of FIG. 4, along line 5-5′.

FIG. 6 illustrates a schematic diagram of one embodiment of a generatorassociated with a sample sectioning device.

FIG. 7 illustrates a schematic diagram of another embodiment of agenerator associated with a sample sectioning device.

FIG. 8 illustrates a schematic diagram of another embodiment of agenerator associated with a sample sectioning device.

FIG. 9 illustrates a schematic diagram of another embodiment of agenerator associated with a sample sectioning device.

FIG. 10 illustrates a schematic diagram of another embodiment of agenerator associated with a sample sectioning device.

FIG. 11 illustrates a block diagram of one embodiment of a samplesectioning device that a sample holder is associated with.

FIG. 12 illustrates a perspective view of one embodiment of a microtomestorage member.

FIG. 13 illustrates another perspective view of the microtome storagemember of FIG. 12.

FIG. 14 illustrates a perspective view of another embodiment of amicrotome storage member.

FIG. 15A illustrates a perspective view of another embodiment of amicrotome storage member.

FIG. 15B illustrates a perspective view of the microtome storage memberof FIG. 15A.

FIG. 16A illustrates a perspective view of another embodiment of amicrotome storage member.

FIG. 16B illustrates a perspective view of another embodiment of amicrotome storage member.

FIG. 17A illustrates a perspective view of one embodiment of a wasteremoval assembly.

FIG. 17B illustrates a cross-sectional side view of the waste removalassembly of FIG. 17A.

FIG. 18-FIG. 20 illustrate perspective views of an embodiment of a wasteremoval assembly.

FIG. 21 illustrates a perspective view of an embodiment of a hand wheellock associated with the sample sectioning device of FIG. 1.

FIG. 22 illustrates a perspective view of an embodiment of a controlpanel associated with the sample sectioning device of FIG. 1.

FIG. 23 illustrates a block diagram of one embodiment of a process forcontrolling a light source based on a sample characteristic.

DETAILED DESCRIPTION

In the following description, numerous specific details, such asparticular microtomes, particular cutting drive systems, particularsensors, particular sensing mechanisms, particular surface orientationmeasurement and/or adjustment processes, and the like, are set forth.However, it is understood that embodiments of the invention may bepracticed without these specific details. In other instances, well-knownmechanical components, circuits, structures and techniques have not beenshown in detail in order not to obscure the understanding of thisdescription.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention.Spatially relative terms, such as “beneath”, “below”, “lower”, “above”,“upper”, and the like may be used herein for ease of description todescribe one element's or feature's relationship to another element(s)or feature(s) as illustrated in the figures. It will be understood thatthe spatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if the device in thefigures is turned over, elements described as “below” or “beneath” otherelements or features would then be oriented “above” the other elementsor features. Thus, the exemplary term “below” can encompass both anorientation of above and below. The device may be otherwise oriented(e.g., rotated 90 degrees or at other orientations) and the spatiallyrelative descriptors used herein interpreted accordingly.

As used herein, the singular forms “a”, “an”, and “the” are intended toinclude the plural forms as well, unless the context indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising” specify the presence of stated features, steps,operations, elements, and/or components, but do not preclude thepresence or addition of one or more other features, steps, operations,elements, components, and/or groups thereof.

The terms “or” and “and/or” as used herein are to be interpreted asinclusive or meaning any one or any combination. Therefore, “A, B or C”or “A, B and/or C” mean “any of the following: A; B; C; A and B; A andC; B and C; A, B and C.” An exception to this definition will occur onlywhen a combination of elements, functions, steps or acts are in some wayinherently mutually exclusive.

FIG. 1 illustrates a schematic view of an embodiment of a microtome orother sample sectioning device. Microtome 100 may be a manual microtome,while in another embodiment, microtome 100 may be an automatedmicrotome. Microtome 100 may include an enclosure or housing 102dimensioned to support and/or enclose various microtome components. Forexample, housing 102 may be a shell like structure, which defines aninterior enclosed space or chamber, within which microtome componentscan be positioned and enclosed, and an outer surface for supportingmicrotome components. The housing 102 may include a base member 104, atop portion 106 and a front portion 108. The base member 104 isdimensioned to rest on a surface, such as a table, upon which the deviceis to be operated, and can support various sample sectioning instrumentsor components. The top portion 106 may be the upper most surface of themicrotome housing 102, and in some cases, provide an area for storage ofmicrotome accessories, as will be discussed herein. The front portion108 connects the top portion 106 to the base member 104, and may supportvarious sample sectioning components. For example, the sectioningassembly 110, which includes various components, instruments, or thelike for sample sectioning, may be mounted to front portion 108 ofhousing 102. Representatively, sectioning assembly 110 may include acutting mechanism 112 mounted to base member 104 and a sample holder 114mounted to front portion 108 of housing 102. Sample holder 114 may bedimensioned to receive and hold a sample (e.g., a paraffin embeddedtissue sample) during a cutting operation.

In addition, to facilitate viewing of the sample during a cuttingoperation, sample holder 114 may further include a light source 116.Light source 116 is configured to illuminate the sample 126 held withinsample holder 114 from a back side (e.g., side facing and/or contactingsample holder 114) so that the user can more clearly see various aspectsof sample 126 during a cutting operation. For example, the sample 126could be a biological tissue that is taken from the body and embedded inparaffin wax. The tissue may include DNA, proteins, lipids,carbohydrates, fibers, connective tissue, or other types of tissuecompounds or structures that can be highlighted, or otherwise made morevisible, by the light source 116 shining there through. In addition, thelight source 116 may help to highlight a location of the tissue withinthe paraffin wax so that the user can, for example, see whether thetissue is being sliced and/or how many more slices of the paraffin arenecessary to reach the tissue. The light source 116 may be controlledusing input devices 130 connected to microtome 100. Input devices 130may, for example, be knobs, buttons, touch pads, or any other user inputdevice that may be used to control an operation of an electroniccomponent. The sample holder 114 and light source 116 configuration willbe describe in more detail in reference to FIG. 2-FIG. 5.

Cutting mechanism 112 may include a cutting member such as a knife orblade 124 suitable for cutting slices of a sample 126 held within thesample holder 114. In one embodiment, sample holder 114 moves relativeto cutting mechanism 112. For example, sample holder 114 may be coupledto a feed drive system or cutting drive system that is operable to movesample holder in a vertical direction (e.g., up and down with respect tohorizontal) while cutting mechanism 112 remains stationary.Alternatively, sample holder 114 (or portions of sample holder 114) mayremain stationary while cutting mechanism 112 is moved, for example in avertical direction (e.g., up and down) with respect to sample holder114. Regardless of which component is moved, the movement of sampleholder 114 with respect to cutting mechanism 112 should be such that itcauses the sample held within sample holder 114 to be sliced orsectioned. More specifically, a surface of sample 126 may besufficiently aligned parallel with cutting mechanism 112 and/or acutting plane associated with cutting mechanism 112 and then sampleholder 114 (or cutting mechanism 112) moved up and/or down to producesufficiently evenly cut sample sections. It should be noted that termssuch as “horizontal”, “vertical”, “top”, “bottom”, “upper”, “lower”, andthe like, are used herein to facilitate the description of theillustrated device. It is possible for other devices to replacehorizontal movements with vertical movements, etc.

The sliced sample sections from sample 126 may be received by, forexample, a sloped receiving member 128 coupled to blade 124. Sectioningassembly 110 may further be designed so that debris or waste (e.g.,pieces of paraffin) associated with the slicing operation may fallbehind cutting mechanism 112 and/or receiving member 128, and onto awaste removal assembly 120 positioned on base member 104, below sampleholder 114. Waste removal assembly 120 will be described in more detailin reference to FIG. 17A-FIG. 20.

Microtome 100 may further include a storage member 122. Storage member122 may include compartments or recessed regions that are designed tohold various microtome components. For example, storage member 122 maybe configured to hold a tissue box, a slide, a carrier holding multipleslides or other instruments such as brushes or pencils a user may needwhile operating microtome 100. Storage member 122 may be integrallyformed with the top portion 106 of microtome housing 102, may be aseparate tray like structure that is removable attached to top portion106, or a combination of an integrally formed member and a removablestructure. Storage member 122 will be described in more detail inreference to FIG. 12-FIG. 16B.

Referring again to FIG. 1, the movement of sample holder 114 may becontrolled using hand wheel 118 (or a control device in the case of anautomated microtome). It should be understood that while only the handleportion of hand wheel 118 can be seen from this view, the handle portionis associated with a wheel that may be rotated upon rotation of thehandle. Rotation of hand wheel 118 may cause a vertical drive memberassociated with sample holder 114 (or cutting mechanism 112) to move ina vertical direction to facilitate slicing of sample 126. In someembodiments, hand wheel 118 may be associated with a generator that isoperable to convert a mechanical energy of hand wheel 118 intoelectrical energy to drive, for example, an operation of light source116. Various aspects of hand wheel 118 and a generator will be discussedin more detail in reference to FIG. 6-FIG. 10.

The specific aspects of sample holder and the associated light sourcewill now be described in more detail in reference to FIG. 2, FIGS.3A-3B, FIG. 4 and FIG. 5. In particular, FIG. 2 illustrates aperspective view of sample holder 114. Sample holder 114 may beconsidered part of, or may itself be, a microtome chuck. Sample holder114 may include a sample receiving portion 202 dimensioned to receiveand hold a sample, and a mounting portion 204 dimensioned to removablymount, or mate, sample holder 114 to the desired microtome. Samplereceiving portion 204 may include a sample receiving surface 206 uponwhich the sample is to be positioned. The sample receiving surface 206may be flanked by a top clamping portion 208 and a bottom clampingportion 210 which define a recessed region 216 within which the samplecan be positioned. The top clamping portion 208 and the bottom clampingportion 210 may be considered part of clamping member 212. Clampingmember 212 also includes a handle 214 that can be used to slide clampingportions 208, 210 toward or away from one another to change a size ofthe recessed region 216 within sample receiving portion 202, and inturn, clamp onto a sample positioned within recessed region 216. Forexample, during operation, the top and bottom clamping portions 208, 210are caused to slide toward one another (e.g., along rails) by pivotinghandle 214 along arrow 218 in a direction away from portion 202 to afirst, extended position (as shown). In this position, portions 208, 210create a recessed region 216 that is approximately same size as, orslightly smaller than, the sample, such that portions 208, 210 (whichare biased toward one another) press against the sample edges, and holdthe sample within recessed region 216. To release the sample fromrecessed region 216 of sample receiving portion 202, handle 214 is movedto a second, retracted position (e.g., pushed or pivoted forward alongarrow 218), so that the top and bottom clamping portions 208, 210 slideaway from one another, thereby increasing the size of the recessedregion 216 and allowing for the sample to be removed. In other words,the pivoting movement of handle 214 forward or backward, in turn, drivesa sliding movement of clamping portions 208, 210 away or toward oneanother, respectively. This movement in turn, further locks the samplewithin, or releases the sample from, recessed region 216 of samplereceiving portion 202. It should be noted that while the illustratedposition of handle 214 (e.g., the extended position) is described hereas a position which causes portions 208, 210 to move away from oneanother, it is also contemplated that this position of handle 214 may,in other cases, move portions 208, 210 toward one another, to clamp asample therebetween.

Light source 116 is positioned along sample receiving portion 202.Representatively, in one embodiment, light source 116 includes a lightemitting chip, for example, one or more of a light-emitting sensor orlight-emitting diode (LED) die or chip including one or more of alight-emitting diode (LED). The LED chip may be positioned along asurface of sample receiving portion 202, or within a cavity or recessformed within sample receiving portion 202. The light source 116 istherefore behind the sample when the sample is positioned within samplereceiving portion 202. The light output by the LED passes through thesample and illuminates the sample from the back side, allowing for thevarious features of a biological tissue therein to be more easilyexamined. The specific aspects of light source 116 and the illuminationof the sample from the back side is shown in FIG. 3A-FIG. 3B.

Representatively, FIG. 3A is a cross-sectional side view, and FIG. 3B isa perspective view, of one embodiment of the sample holder of FIG. 2.FIG. 3A illustrates an embodiment in which light source 116 ispositioned within a cavity 302 of the receiving surface 206 of samplereceiving portion 202. In particular, cavity 302 is open to receivingsurface 206, and formed by a sidewall 306 and a bottom wall 304 whichare formed behind (or otherwise in a different plane than), receivingsurface 206. Accordingly, when sample 126 is positioned on, andcontacts, receiving surface 206, the light source 116 is consideredbehind sample 126. In other words, the light source 116 is betweensample 116 and the bottom wall 302 of cavity 302. In this aspect, thelight beam or ray 308 emitted by light source 116 is transmitteddirectly to, and contacts, the back side 310 of sample 116, and passesthrough sample 116, to the front side 312. By “directly” it is meantthat the light beam or ray 308 is directed to, and reaches, the sample116 without having to be redirected or refocused toward the sample 116,such as by an intervening optical element or reflective element. Inaddition, it should be recognized that because the light source 116 is arelatively low profile light source, such as an LED chip, light source116 can rest against the bottom wall 302 of cavity 302 without extendingbeyond the plane of the receiving surface 206 upon which sample 126rests. For example, in some embodiments, the height of sidewall 306 ofcavity 302, and therefore the overall depth of cavity 302, can besubstantially the same as a thickness of light source 116 (e.g., an LEDchip), such that a planar, light emitting surface, of light source 116is within a same plane, or substantially the same plane, as receivingsurface 206. Said another way, cavity 302 is considered a relativelyshallow cavity in that the length (l) of the bottom wall 304 is lessthan the height (h) of the side wall 306. Due to the dimensions ofcavity 302 and light source 116, sample 126 can be positioned in closeproximity to light source 116, and the associated light beam or ray 308,thus avoiding any unnecessary space or gap between the light source 116and sample 126 through which light beam or ray 308 could leak through,and thereby result in less of the light beam or ray 308 reaching sample126. It should further be understood that, in some embodiments, cavity302 while being open to receiving surface 206, is closed to the backside of sample receiving portion 210, such that it does not extendentirely through portion 210. In this aspect, the entire light source116 is considered closer to receiving surface 206, and in turn sample126, than the back side of sample receiving portion 210. It isrecognized, however, that while cavity 302 is illustrated and describedas being formed in receiving surface 206, in some embodiments, it couldbe formed within any wall of the sample holder, for example a sidewall(e.g., a surface of member 208 or 210 facing the side of sample 126) sothat it transmits light into a side of sample 126 that is not resting onsurface 206.

In addition, in some embodiments, the surface area of light source 116can be selected to cover a desired surface area of sample 126 so thatmaximum illumination of sample 126 is achieved. For example, lightsource 116 may have a surface area sufficient to illuminate an entiresurface area of front side 312 of sample 126. Representatively, in oneembodiment, light source 116 may have a substantially square orrectangular shaped light emitting surface area, and sample 126 may havea similar shape such that illumination of the sample 126, including thecorners, is maximized. It should further be noted that the term “sample”is generally used to refer to, for example, a carrier 314 and abiological sample 316, such as a tissue, contained within the carrier314. For example, the term “sample” could generally include a biologicaltissue 316 as well as the carrier 314, within which the biologicaltissue 316 is contained. The biological tissue 316 could be any type ofbiological material from a multicellular organ, for example, a bulktissue and/or an aggregate of cells and cell products that together forma structural material having a particular function. For example, tissue316 could be a tissue taken from the body, and which includes DNA,proteins, lipids, carbohydrates, fibers, connective tissue, or othertypes of tissue compounds or structures that can be highlighted, orotherwise made more visible, by the light source 116 shining therethrough. The carrier 316 could include a paraffin block, and in somecases a paraffin block positioned as well as a cassette within which itis positioned. For example, the cassette could be a plastic cassettethat serves as a supporting structure for the paraffin during theprocess of embedding the biological tissue within the paraffin. In thisaspect, illumination of sample 126, can be understood to mean that thebiological tissue 316 (e.g., tissue), the carrier 314 (e.g., paraffinand/or cassette) and/or both the biological tissue 316 and carrier 314are illuminated. The illumination of the entire sample 126 isillustrated in FIG. 3B.

Still further, in some embodiments, both an intensity or brightness andcolor or wavelength of the light output by the light source 116 may becontrolled and modified depending on, for example, characteristics ofthe sample to be sliced. For example, in one embodiment, the lightsource 116 is an LED chip operable to output light of one, or a numberof different colors. For example, the light source 116 may be an LEDchip that includes a number of LEDs fabricated on, or otherwiseelectrically connected to, a semiconductor block or wafer (including acircuit). For example, the LED chip may include one or more LEDs thatoutput different colored light, for example, light at wavelengths withina range of about 360 nanometers (nm) to about 425 nm (e.g., UV LEDs),from about 430 nm to about 505 nm (e.g., blue LEDs), from about 515 nmto about 570 nm (e.g., green LEDs), from about 585 nm to about 595 nm(e.g., yellow LEDs), 630 nm-660 nm (e.g., red LEDs) and from about 2200Kelvin (K) to about 10000K (e.g., white LEDs). These different coloredLEDS can be individually controlled, and in some cases theircorresponding light output mixed, to produce the desired light coloroutput. For example, two or more colored LEDs (e.g., primary LEDs) couldbe mixed to produce a single colored light output (e.g., a white light).Alternatively, an LED of a single color (e.g., white) could be operatedalone while the other LEDs are turned off (e.g., primary LEDs), toachieve a desired color output. In addition, the intensity or brightnessof one or more of the LEDs can be independently controlled or modifiedwithin a range of from about 50 millicandela (mcd) to about 15000 mcd.For example, an intensity or brightness of one LED (e.g., a red LED)could be increased while the intensity or brightness of another LED(e.g., a green LED) reduced, where a red output is desired. For example,an LED which outputs the desired color could be increased to abrightness or intensity of from about 1000 mcd to about 1500 mcd, whilethe intensity or brightness of an LED of a color that is not desiredcould be decreased to within a range below that of the desired coloredLED, for example, a range of from about 50 mcd to about 1000 mcd. Itshould further be understood that although the adjustment of twoexemplary LEDs is discussed, an intensity of brightness of more thantwo, for example, three, four, or more LEDs could be adjusted at thesame time, consecutively or at different times to achieve a desiredlight output. In other words, they are all independently controlledtherefore any combination of colors and/or intensity/brightness can beachieved depending on the desired output.

The intensity, brightness and/or color of the light output may bemanually selected by the user, or automatically selected by a microtomecontroller depending upon, for example, a characteristic of the sample.For example, the sample characteristic may be a color or density of thetissue or features within the tissue (e.g., biological components suchas DNA, proteins, lipids, carbohydrates, fibers, connective tissue, orthe like), or a color or density of the medium in which the tissue isembedded (e.g., paraffin). In particular, the color or brightness of thelight output by light source 116 can be modified to create more contrastbetween the tissue or characteristics of the tissue and the surroundingmedium (e.g., paraffin). This may be achieved by, for example, modifyingan intensity or brightness of one of the LEDs with respect to another ofthe LEDs so that a desired light output color is achieved. For example,where it is determined based on the sample that a blue light outputwould allow for better viewing of the sample, the intensity of a bluewavelength LED could be increased while the intensity of a redwavelength LED, green wavelength LED and/or yellow wavelength LED couldbe reduced, or turned off all together.

In addition, in still further embodiments, the characteristic of thesample may be a color of a cassette holding the paraffin embeddedtissue. For example, in one embodiment, the cassette may be a cassettehaving a particular color (e.g., red, orange, yellow, blue, green,purple, pink, brown, etc.). In this aspect, when the light source 116emits a white light through openings (or grills) in the cassette, theparaffin surrounding the tissue may appear the color of the cassette.For, example, the cassette may be a red cassette from the Tissue-Tek®III Uni-Cassette® System available from Sakura Finetek Europe B.V.,which has grills or openings to allow for fluid exchange during tissueprocessing operations. When light source 116 emits a white light throughthe sample, the red color of the cassette may cause the paraffin toappear red to the viewer. To compensate for this color change due to thecolor of the cassette, the red, green and/or blue intensity of the whitelight can be individually controlled to decrease the intensity of thecolor of the light reflected by the red cassette, so that the paraffinappears white again.

One exemplary process for controlling the output of the light source 116based on a characteristic of the sample is illustrated in FIG. 23.Representatively, in one embodiment, process 2300 includes the operationof determining a characteristic of the sample (block 2302). Thecharacteristic of the sample may be, for example, a color or density ofthe tissue or features within the tissue, a color or density of themedium in which the tissue is embedded (e.g., paraffin), a color of thecassette within which the paraffin embedded tissue is held, or in somecases, a color of the paraffin. This characteristic may be determinedmanually (e.g., a user observing a characteristic of the sample), orautomatically (e.g., a scanner reading an identifier associated with thesample that contains the information about the sample characteristic).Based on this information, the light output by light source 116 may thenbe adjusted or controlled to illuminate the sample as desired. Forexample, as previously discussed, in an embodiment where the cassette isred (or another color), the red, green and/or blue intensity of thewhite light can be individually controlled to decrease the intensity ofthe color of the light reflected by the red cassette, so that theparaffin appears white again.

Returning now to further aspects of light source 116, light source 116may be electrically connected to a microtome, and its associatedelectronic components and/or a power source, by circuitry within sampleholder 114. Representatively, as can be seen from the back side view ofsample holder 114 illustrated in FIG. 4, and the bottom section view ofFIG. 4, along line 5-5′ as illustrated in FIG. 5, sample receivingportion 202 of sample holder 114 is mounted to, or otherwise includes,mounting portion 204. Mounting portion 204 may be any type of mountingmember suitable for mounting, or otherwise connecting, sample holder 114(e.g., the chuck) to the microtome, as previously discussed.

More specifically, as seen from the cross-sectional view of FIG. 5,sample holder 114 includes an internal chuck clamping member 406.Internal chuck clamping member 406 may include biasing members 510(e.g., springs) and be part of clamping member 212, for example,connected to clamping portions 208, 210 (see FIG. 2) to facilitateclamping of the sample within receiving portion 202. The clamping member406 is positioned within a channel 512 formed within sample receivingportion 202, and behind light source 116. In this aspect, clampingmember 406 may be considered directly behind light source 116. Theregion of channel 512 between light source 116 and clamping member 406may be used to support a flexible circuit 402 that electrically connectslight source 116 to a source of power. For example, flexible circuit 402may be positioned over the portion of clamping member 406 facing lightsource 116. Flexible circuit 402 may be electrically connected at oneside to light source 116 by electrical contacts (not shown) associatedwith light source 116. The flexible circuit 402 may be electricallyconnected at another side to electrical contacts 404 of mounting portion204, which electrically connect to circuitry 516 and a power source 518.Circuitry 516 may be any type of circuitry operable to process, control,and/or execute instructions, a processing protocol, or the like used foroperation of a microtome (e.g., a light source operation). Power source518 may be any type of power source operable to provide power to themicrotome components (e.g., the light source), for example, a generator,AC power supply, battery power or the like. In this aspect, light source116 may be electrically connected to electrical contacts 404 of mountingportion 204, and in turn receive instructions and/or power to operatethe light source 116, via flexible circuit 402. It is to be understoodthat although a flexible circuit is illustrated, light source 116 may beelectrically connected to electrical contacts 404 in any suitable matter(e.g., wires or the like).

The mounting portion 204 of sample holder 114 may then be mounted to aportion of the microtome (e.g., front portion 108 of housing 102) withcorresponding electrical contacts or terminals that make contact withelectrical contacts 404 within mounting portion 204. For example,mounting portion 204 may have a mating portion (e.g., groove,protrusion, track, channel or the like) complementary to a matingportion of the device it is to be mounted to (e.g., a microtome) suchthat it can, in one aspect, be mounted to the device, and in anotheraspect, removed from the device. The corresponding electrical contactsor terminals of the microtome may be associated with a power source(e.g., an outlet, a battery, a generator or the like) or other circuitryused to provide power to and/or control an operation of light source 116as previously discussed, more specifically each LED making up lightsource 116 individually. In this aspect, because sample holder 114 isnot hard wired into the microtome itself, it can be removed and mountedto any microtome having a corresponding electrical contact suitable forproviding power and/or signals to light source 116.

FIG. 6, FIG. 7, FIG. 8 and FIG. 9 illustrate schematic views of variousenergy harvesting mechanisms that may, in one embodiment, be used tosupply power to light source 116, or any other electronic componentsassociated with sample holder 114 (e.g., an alarm). Representatively, inembodiments where microtome 100 is a manual microtome, there is noactive power source (e.g., electrical current) associated with themicrotome to, for example, drive movement of the sample holder 114during a slicing operation. Rather, rotation of the hand wheelmechanically drives, for example, the up and down movement of sampleholder 114 with respect to the cutting mechanism to slice the sample.Similarly, because the microtome is completely manual, there is no powersource for operation of light source 116. Therefore, in one embodiment,microtome 100 further includes an energy harvesting mechanism forgenerating power (in the absence of electrical energy), that can be usedfor operation of light source 116, and in some cases, can be stored forlater operation of light source 116. The energy harvesting mechanism maybe any type of system capable of converting one form of energy (e.g.,mechanical, motive or solar energy) into an electrical energy that canbe used to power light source 116, and any other components associatedwith the microtome that may require an electrical input (e.g., analarm).

Representatively, FIG. 6 illustrates a schematic view of one embodimentwhere the energy harvesting mechanism is a generator 600 that cangenerate electricity from the rotation of a hand wheel 602 associatedwith the microtome (see also hand wheel 118 previously discussed inreference to FIG. 1). Representatively, the hand wheel 602 may include ahandle 604 connected to disc 606 that rotates as shown by arrow 608 uponrotation of handle 604. To facilitate energy generation, the disc 606may include a magnetic strip 610 arranged in series along its outer edgeand a rotating magnetic core 612 that is magnetically coupled with disc606. The magnetic core 612 may, in turn, include coils 614 within whichan electric current can be generated when magnetic core 612 is rotatedwith respect to magnetic strip 610. This electric current or voltage is,in turn, transmitted from coils 614 to circuitry 616 (e.g., processingcircuitry or a controller) and ultimately to light source 116 (e.g., bythe electrical contacts 404 of mounting portion that are connected toflexible circuit 402). In this aspect, generator 600 uses the rotationof hand wheel 602 to generate an electric current or voltage that canthen be carried to light source 116 via circuitry as previouslydiscussed. It should be understood that since, in this embodiment, disc606 must be rotating to generate the electric current, in someembodiments, a storage module may further be provided so that theelectricity can be stored and used at a later time (e.g., on demand suchas by pressing a button or operating a switch), without having to rotatedisc 606.

FIG. 7 illustrates a schematic view of another embodiment of a microtomegenerator. In this embodiment, generator 700 includes a microtome handwheel 602 having a handle 604 coupled to a disc 606. Handle 604 can beused to rotate disc 606 as shown by arrow 608 to actuate, for example, acutting operation, as previously discussed. In this embodiment, however,disc 606 is coupled to a smaller wheel 702 that is coupled to a steppermotor 706 to generate an electric current. In particular, rotation ofdisc 606 (such as by rotation of handle 604) causes a rotation ofsmaller wheel 702 as shown by arrow 704, which is coupled to steppermotor 706 by axle 708, and in turn, drives stepper motor 706 andgenerates an electric current or voltage. The stepper motor 706 may becoupled to circuitry 616 which can be used to transmit the generatedcurrent or voltage to light source 116 to provide power to light source116. Similar to generator 600, generator 700 may also be coupled to astorage module that can store the electrical current or voltage, so thatit can be used at a later time to power light source 116.

FIG. 8 illustrates a schematic view of another embodiment of a microtomegenerator. In this embodiment, generator 800 is substantially similar togenerator 700 described in reference to FIG. 7, except in thisembodiment, a belt 802 is coupled to the smaller wheel 702 to rotatesmaller wheel 702 when disc 602 is rotated (e.g., using handle 604), andgenerate electricity using stepper motor 706. In particular, belt 802encircles disc 606 and the smaller wheel 702. Rotation of disc 606causes belt 802 to rotate smaller wheel 702, and in turn, stepper motor706 generates a voltage that can be used to power light source 116. Forexample, the stepper motor 706 is coupled to circuitry 616 (and in somecases storage), which facilitates transmission of the electric currentor voltage to light source 116, as previously discussed.

FIG. 9 illustrates a schematic view of another embodiment of a microtomegenerator. In this embodiment, generator 900 includes a rack and pinionarrangement that is used to generate an electric current or voltageusing a stepper motor. In particular, rotation of hand wheel 602 aspreviously discussed, causes a shaft 902 associated with sample holder114 to move up and down as illustrated by arrow 904. Shaft 902 contactsrack 908, which is positioned near shaft 902, causing rack 908 to alsomove up and down, as illustrated by arrow 910. Rack 908 is coupled topinion 906 of stepper motor 706. The movement of rack 908, therefore, inturn, causes pinion 906 to rotate, and drive stepper motor 706associated with pinion 906, which in turn, generates an electric currentor voltage. The stepper motor 706 is coupled to circuitry 616 (and insome cases storage), which facilitates transmission of the electriccurrent or voltage to light source 116, as previously discussed.

FIG. 10 illustrates a schematic view of another embodiment of amicrotome generator. In this embodiment, generator 1000 includespiezoelectric material 1002 that is used to generate an electric currentor voltage. Representatively, in this embodiment, generator 1000includes a piezoelectric material 1002 which is either compressed orexpanded by shaft 902 as it moves up and down as illustrated by arrow1004, as previously discussed. This, in turn, cause the piezoelectricmaterial 1002 to generate an electrical charge corresponding to anelectric current or voltage. The piezoelectric material 1002 is coupledto circuitry 616 (and in some cases storage), which facilitatestransmission of the electric current or voltage to light source 116, aspreviously discussed.

It should be understood that in any of the previously discussedembodiments, the voltage or electric current produced by the generatorcan be used to power any component of the microtome so that, forexample, a cutting operation, a processing protocol or the like, may becompleted. For example, in one embodiment, the electric current can beused to turn on/off light source 116, modify a brightness or intensityof light source 116, or modify a color or wavelength of light source116, as previously discussed. In addition, it should be understood thatin embodiments where the light source 116 includes a number of LEDs, thevoltage or electric current can be used to operate or otherwise control(e.g., turn on/off, modify a brightness or intensity, or modify a coloror wavelength) each of the LEDs individually. In addition, in someembodiments, microtome 100 further includes a storage module, forexample a battery or capacitor, that can be used to store the voltageproduced by the generator and used to provide power to light source 116when the hand wheel is not being rotated. In this aspect, light source116 can be used not only during a cutting operation in which hand wheelis being rotated, but also when hand wheel is not being rotated. Inaddition, the voltage can be used to provide power to other electroniccomponents that may be associated with the microtome. For example, theelectronic component may be an alarm (see alarm 1116 of FIG. 11) thatlights up, vibrates or makes a noise when the hand wheel is beingrotated to alert a user that a cutting operation is being performed. Inthis aspect, an alarm that could typically not be used with a manualmicrotome because there is no power source, can now be used to alert theuser. It should be recognized that although the alarm is described asbeing used to alert the user of a cutting operation, it may be used toalert the user of any information desired during operation of amicrotome (e.g., completion of a cutting cycle, presence/absence of asample, low power, etc.).

As previously discussed, the slicing operation may proceed manuallythrough user interaction with the system, or in some cases,automatically. FIG. 11 illustrates a schematic block diagram of oneembodiment of a microtome including a hand wheel, a generator andprocessing circuitry for controlling an operation of the light sourceassociated with the sample holder. Representatively, device 1100 mayinclude processing circuitry 1102, a power source 1104 and input-outputdevices 1110 and be associated with sample holder 1118. Processingcircuitry 1102 may be used to control the operation of a light source1120 associated with sample holder 1118, or other electronic componentsassociated with device 1100 (e.g., an alarm). Processing circuitry 1102may be based on a processor such as a microprocessor and other suitableintegrated circuits. With one suitable arrangement, processing circuitry1102 may be used to run, for example, software on device 1100 whichcontrols an operation of light source 1120 (e.g., on/off, a brightnessor color).

Input-output devices 1110 may be used to allow data and/or instructionsto be supplied to device 1100 and to allow data to be provided fromdevice 1100 to external devices. A hand wheel 1112, buttons 1114 andalarm 1116 are all examples of input-output devices 1110. A user cancontrol the operation of device 1100 by supplying commands through userinput devices such as hand wheel 1112 and buttons 1114. In someembodiments, an optional display and audio devices may be provided,which could include liquid-crystal display (LCD) screens or otherscreens, light-emitting diodes (LEDs), and other components that presentvisual information and status data. Display and audio devices may alsoinclude audio equipment such as speakers and other devices for creatingsound. Display and audio devices may contain audio-video interfaceequipment such as jacks and other connectors for external headphones andmonitors.

Device 1100 may further include power source 1104 for supplying power toelectronic components associated with device 1100 (e.g., a light sourceor alarm). Power source 1104 may include a generator 1106 that, forexample, uses the rotation of hand wheel 1112 to generate electricity,as previously discussed. Power source 1104 may further include a battery1108 or other device such as a capacitor that can store electricalenergy (e.g., energy generated by the generator) for later use. Inaddition, in still further embodiments, power source 1104 may include awall mounted plug-in power supply, for example, in the case of anautomated microtome.

Device 1100 can communicate with external devices, such as sample holder1118 as shown by path 1122. Path 1122 may include a wired or wirelesspaths (e.g., flexible circuit 402 described in FIG. 4-FIG. 5). Sampleholder 1118 may include a light source 1120, and be substantiallysimilar to sample holder 114 and light source 116 previously discussedin reference to FIG. 1-5. In this aspect, an electric current generatedby, for example, generator 1106 may be used to power light source 1120and processing circuitry 1102 may be used to control an operation oflight source 1120 (e.g., control a brightness or color).

FIG. 12-FIG. 16B illustrate perspective views of various embodiments ofa storage member associated with a sample sectioning device such as amicrotome. Representatively, FIG. 12 shows storage member 1200 that isdesigned to store various sample sectioning device accessories onmicrotome 1202. Microtome 1202, may for example, be substantiallysimilar to microtome 100 previously discussed in reference to FIG. 1,which is coupled to a sectioning assembly 110 (e.g., chuck), thereforethe specific features previously discussed in reference to FIG. 1 willbe omitted here. Instead, the various aspects of the associated storagemember 1200 will now be discussed. Representatively, in one embodiment,storage member 1200 may be integrally formed within a top portion ofmicrotome 1202. For example, storage member 1200 may be part of, andinseparable from, the top portion 106 of housing 102 previouslydiscussed in reference to FIG. 1. Representatively, storage member 1200may include recessed regions 1204A, 1204B, 1204C, 1204D and 1204E thatare formed within the top portion (or wall) of the housing of microtome1202. Recessed regions 1204A-1204E may have any size and shape suitablefor receiving and holding microtome accessories therein as shown in FIG.13. Representatively, recessed regions 1204A-1204E may have square orrectangular profiles and be sized to accommodate microtome accessoriessuch as a tissue box 1302, slide carrier 1304, elongated instruments1306 or the like can be positioned on top of microtome and stored therewithout falling off. For example, each of recessed regions 1204A-1204Emay include a base portion 1206 upon which the desired microtomeaccessory can rest, and one or more sidewall(s) 1208 which surrounds thebase portion 1206, and separate one recessed region from anotherrecessed region. Each of the base portion 1206 and sidewall(s) 1208 ofstorage member 1200 may be formed of the same material as the microtomehousing (e.g. a plastic or the like). In some cases, a portion of therecessed regions 1204A-1204E (e.g., base portion 1206) may betexturized, or otherwise have a non-smooth surface or include atexturized mat, to help hold the desired microtome accessory therein.

FIG. 14-FIG. 16B illustrate perspective views of other embodiments of astorage member than can be used in addition to, or instead of, storagemember 1200. It should be noted that for ease of illustration, thevarious interior components of the microtome are omitted in FIG. 14-FIG.16B, however, could also be present. Representatively, storage member1400 in this embodiment, is a tray like structure that is separate fromthe microtome housing and is dimensioned to rest on top of microtome1202, for example, within the recessed regions or cavities formed bystorage member 1200 previously discussed in reference to FIG. 12-FIG.13. Storage member 1400 can rest on top of microtome 1202, and can alsobe removed from microtome 1202. In this aspect, the contents of storagemember 1400 can be moved to a different location than microtome 1202(e.g., off to the side of microtome), while still maintaining the samearrangement and/or position so that the user can easily locate eachaccessory.

In one embodiment, storage member 1400 may have a receiving member 1402,that is designed to store microtome accessories, and a support member1408 that is designed to help hold the storage member 1400 on microtome1202, and may also be used for storage. In this aspect, receiving member1402 may include a storage surface 1404 and a mating surface 1406.Storage surface 1404 may be a top side of receiving member 1402 (e.g., aside that faces away from the microtome) and include various recessedregions or cavities 1410A, 1410B, 1410C dimensioned to retain microtomeaccessories (e.g., tissue box, slide carrier, slides, elongatedinstruments or the like). Mating surface 1406 is formed by an oppositeside of receiving member 1402 and is dimensioned to mate with recessesformed on a top portion of microtome 1202 (e.g., recessed regions1204A-1204E). For example, mating surface 1406 may include protrudingportions that are complimentary to recesses or cavities along the topportion of microtome 1202 (e.g., within storage member 1200) and fitwithin the cavities to hold storage member 1400 in place.

Support member 1408 may extend from receiving member 1402 and overlap aside of microtome 1202 as shown to help hold storage member 1400 inplace. In particular, support member 1408 may include a first portion1412 that is substantially flat, planar or curved, and extends from anedge of receiving member 1402 (e.g., horizontally), and a second portion1414 that is at an angle to first portion 1412 such that it extends in adownward direction (e.g., vertically) along the side of microtome 1202.In other words, second portion 1414 is at an angle with respect to firstportion 1412. For example, second portion 1414 may be considered tocurve around an edge of microtome 1202 and downward from first portion1412. Support member 1408 may further include a cavity or channel 1416that can also be used to store microtome accessories along a side ofmicrotome 1202 as shown. The cavity or channel 1416 may have anelongated profile and extend along a portion of the side of microtome1202.

FIG. 15A illustrates a perspective view of another embodiment of astorage member. Storage member 1500 shown in FIG. 15A is substantiallysimilar to storage member 1400, except in this embodiment, the cavities1410A-1410C are arranged differently along receiving member 1402. FIG.15B illustrates a perspective view of storage member 1500 with themicrotome accessories removed so that cavities 1410A-1410C can be moreclearly seen. In particular, from this view, it can be seen, forexample, that recessed region or cavity 1410B includes a number of slots1502, which are dimensioned to receive and hold a microscope slidewithin cavity 1410B. Representatively, the slots 1502 may have walls,which are evenly spaced from one another and form cavities (about thedistance of a slide) dimensioned to hold the microscope slides next toeach other, on their sides, and in some cases, at a slight angle.Cavities 1410A and 1410C may further be formed by recessed regionsdefined by side walls 1504.

FIG. 16A and FIG. 16B illustrate perspective views of another embodimentof a storage member. Representatively, FIG. 16A illustrates aperspective view of another embodiment of a storage member than can beused in addition to, or instead of, storage member 1200, and FIG. 16Billustrates the storage member of FIG. 16A positioned on top of amicrotome. Representatively, storage member 1600 in this embodiment, isa tray like structure that is dimensioned to rest on top of microtome1202, for example, within the recessed regions or cavities formed bystorage member 1200. Storage member 1600 may have a receiving member1602, which is designed to store microtome accessories, and a supportmember 1608, which is designed to help hold the storage member 1600 onmicrotome 1202, and may also be used for storage.

Receiving member 1602 may include a storage surface 1604 and a matingsurface 1606. Storage surface 1604 may be a top side of receiving member1602 (e.g., a side that faces away from the microtome) and includevarious recessed regions or cavities 1610A, 1610B, 1610C dimensioned toretain microtome accessories (e.g., tissue box, slide carrier, slides,elongated instruments or the like). Mating surface 1606 is formed by anopposite side of receiving member 1602 and is dimensioned to mate withrecesses formed on a top portion of microtome 1202. For example, matingsurface 1606 may include protruding portions that are complimentary torecesses or cavities along the top portion of microtome 1202 (e.g.,within storage member 1200) and fit within the cavities to hold storagemember 1600 in place.

In some embodiments, cavities 1610C may have slots to retain slides 1620(see FIG. 16B), therein (e.g., slots 1502 as previously discussed) andfurther include openings 1612 to allow for liquids to drip throughstorage member 1600. For example, the cavities 1610C may form a dryingrack for microtome accessories such as slides 1620 (see FIG. 16B), whichmay have a liquid component (e.g., water) that drains off the slide whenit is positioned in the rack. Openings 1612 allow for the liquid todrain through member 1600 and not collect within the bottom of thecavities 1610C where it could, for example, be a source for bacterialgrowth and contaminate the slides. In addition, as shown in FIG. 16B,cavity 1610A may be dimensioned to receive an accessory such as acontainer 1622 (e.g., tissue box, slide container, or the like).

In some embodiments, a liquid absorbing member 1614 may further bepositioned between storage member 1600 the surface of microtome 1202,for example, within recessed region of storage member 1200. In thisaspect, when storage member 1600 is placed within member 1200 as shownin FIG. 16B, any liquid that flows through openings 1612 is collectedand absorbed by liquid absorbing member 1614. Liquid absorbing member1614 may be any type of liquid absorbing member, for example, a tissue,a napkin, a paper towel, a piece of cloth, or the like.

In addition, storage member 1600 may further include support member 1608which extends from receiving member 1602 and overlaps a side ofmicrotome 1202 as shown in FIG. 16B to help hold storage member 1600 inplace. Support member 1608 may include a cavity or channel 1616 that canalso be used to store microtome accessories along a side of microtome1202 as shown, as well as other similar features as previously discussedin reference to storage member 1400 of FIG. 14.

As can also be seen from FIG. 16A and FIG. 16B, microtome 1202 mayinclude knobs 1618 to control the operation of light source 116 aspreviously discussed in reference to, for example, FIG. 1 to FIG. 5.

FIG. 17A-FIG. 18 illustrate perspective views of a waste removalassembly for a sample sectioning device. Referring to FIG. 17A-17B,waste removal assembly 1700 may be configured to facilitate removal ofwaste, such as paraffin debris, that falls onto the surface of microtome100 during a cutting operation. Microtome 100 may, for example, besubstantially similar to microtome 100 described in reference to theprevious Figures. Thus, while specific details of microtome 100 are notdescribed and/or shown in FIG. 17A-FIG. 18, it should be understood thatthey may be included.

Removal assembly 1700 may be positioned on base member 104 of microtome100, below cutting mechanism 112 and sample holder 114. In this aspect,when sample 126 is sliced by cutting mechanism 112, the sliced samplesection remains on the front side of cutting mechanism 112 (e.g., sidefacing away from base member 104) and any waste falls behind cuttingmechanism 112 onto waste removal assembly 1700. Typically, any waste ordebris that falls into this area of microtome 100 is difficult to removebecause it is between cutting mechanism 112, the front side ofmicrotome, and sample holder 114, and is therefore difficult for theuser to reach.

Waste removal assembly 1700, however, solves this problem by providing amechanism that helps to push the debris out of this area to a locationwhere it is easier for the user to remove. For example, waste removalassembly 1700 may include a first waste member 1702 and a second wastemember 1704, in some embodiments, first waste member 1702 and secondwaste member 1704 are plates that are at angles, or otherwise inclined,with respect to one another, and the base member 104, such that theyform a pitched surface below sample holder 114. in this aspect, when thewaste falls on first and second waste members 1702, 1704, it slides downthe surface of the members, or can be easily brushed down the surface bythe user, and away from the cutting mechanism 112 so that it can beeasily removed by a user. In one embodiment, first waste member 1702 andsecond waste member 1704 are fixed with respect to one another in thepitched configuration as shown. In other embodiments, first and secondwaste member 1702 and 1704 are movable with respect to one another andhave a modifiable slope that can be increased or decreased to facilitateremoval of debris. For example, in some embodiments, first and secondwaste members 1702 and 1704 are coupled to an actuator that causesmembers 1702, 1704 to move with respect to each other.

For example, FIG. 17B illustrates a cross-sectional side view of thewaste removal assembly 1700 of FIG. 17A. From this view, it can be seenthat an actuator 1710 is connected to second waste member 1704 (and alsoconnected to first waste member 1702 although not seen from this view).The actuator 1710 may further be connected to cutting mechanism 112. Inthis aspect, when cutting mechanism 112 slides along rails 1706, this inturn causes actuator 1710 to slide, and move members 1702, 1704 withrespect to each other, for example from a first (closer to horizontal)position to a second (closer to vertical) position, as illustrated bythe dashed lines. The movement of cutting mechanism 112, actuator 1710and/or operation of members 1702, 1704 may be automated or manual, Forexample, where a movement of cutting mechanism 112 is automated (e.g.,such as in an automated microtome), the movement of actuator 1710 andmembers 1702, 1704 may further be considered automated. In otherembodiments, the movement of cutting mechanism 112, actuator 1710 and/ormembers 1702, 1704 may he done manually such as by a user holding one ormore of these components and moving (e.g., sliding or rotating) them asdesired. The operation of actuator 1710 and members 1702, 1704 will bedescribed in more detail in reference to FIG. 18-FIG. 20.

First waste member 1702 and second waste member 1704 may, in someembodiments, be metal plates. In some embodiments, a temperature of themetal plates can be controlled to facilitate removal of the wastethereon. For example, a thermoelectric cooler (TEC) 1708 may optionallybe coupled to one or both of members 1702, 1704 to maintain a desiredtemperate of members 1702, 1704. For example, it may be desirable tocool members 1702, 1704 below a melting temperature of paraffin, suchthat the waste (which includes paraffin) resting on members 1702 doesnot melt and stick to the members 1702, 1704. In addition, in someembodiments to further facilitate waste removal, members 1702, 1704 mayhave a surface coating (e.g., a non-stick coating such as a fluorocarbonpolymer) that makes the surface smoother, or otherwise easier, for thewaste to slide off of it.

Referring now to FIG. 18-FIG. 20, FIG. 18-FIG. 20 illustrate oneembodiment of an operation of a waste removal assembly having movablefirst and second waste members. Representatively, FIG. 18 shows wasteremoval assembly 1700 in a first position, for example a wastecollecting position, in which an incline of first and second wastemembers 1702, 1704 is minimal, or there is no incline and members 1702,1704 are both within a same plane. Any waste or debris 1806 from acutting operation falls onto first and second waste members 1702, 1704as shown. First and second waste members 1702, 1704 are attached to thebase member 104 (of microtome 100, as previously discussed) at oppositeedges by hinges 1802, 1804, respectively. The interfacing edges 1816,1818 of first and second waste members 1702, 1704, respectively,however, are free and able to move with respect to one another. Anactuating member 1710 (e.g., a beam or other elongated structure)including spaced apart protrusions 1810 is positioned in front of eachof first and second waste members 1702, 1704. The actuating member 1710slides toward or away (e.g., horizontally) from first and second wastemembers 1702, 1704 as shown by arrow 1812 to change the slope or angleof incline of first and second waste members 1702. 1704 with respect tobase member 104. In particular, when actuating member 1710 is pushedtoward first and second waste members 1702, 1704, protrusions 1810 slideunder first and second waste members 1702, 1704 causing them to rotateaway from one another (e.g., rotate outwardly or vertically) which, inturn, increases the slope or angle of incline with respect to basemember 104 (or horizontal) as shown in FIG. 19. Representatively, FIG.19 shows first and second waste members 1702, 1704 rotated to a secondwaste removal position which may be an angle of approximately 90 degreesas shown by angle 1902. Said another way, first and second members 1702,1704 may rotate within an angle of rotation of approximately 90 degrees(e.g., between 0 degrees to 90 degrees). This, in turn, causes wastemembers 1702, 1704 (and the surfaces of waste members 1702, 1704) tohave a substantially vertical orientation, and therefore debris 1806 tofall off first and second waste members 1702, 1704, and away from thecutting mechanism to an area of microtome 100 where it can be moreeasily removed. It is noted, however, that although an angle of rotationof approximately 0-90 degrees is disclosed, a greater angle of rotationin which members 1702, 1704 are beyond vertical, for example, from 0-180degrees, is also contemplated.

Once the debris is removed, actuator 1710 slides away from first andsecond waste removal members 1702, 1704 as shown by arrow 2002 in FIG.20 such that they rotate back to the first waste collection position inwhich the angle of incline 1814 is much smaller than when they are inthe removal position (for example, an angle 1814 less than 90 degrees.

In addition, in some embodiments, the microtome disclosed herein mayfurther include a hand wheel locking mechanism as illustrated by FIG.21. In particular, after moving the sample holder (e.g., sample holder114) using a hand wheel 2102 associated with the sample sectioningdevice (e.g., microtome 100), a locking mechanism 2104 may be engaged tolock the sample holder (e.g., sample holder 114) in the desiredposition. In some embodiments, the locking mechanism 2104 may also beassociated with an indicator light or alarm associated with themicrotome, which can be turned on to indicate that the hand wheel is ina locked position. For example, the locking mechanism 2104 may include atab 2104B that is part of a locking latch 2104A as shown in FIG. 21. Inthe locked position, when the latch 2104A locks the wheel 2102 in place(e.g., by latching to a wheel spoke or other wheel component), the tab2104B activates a photo switch 2106 to send a signal to a controller2108, which in turn, sends a signal to turn on (or off) an indicatorlight 2110 located on the front of the microtome.

FIG. 22 shows one embodiment of an indicator light that may beassociated with the locking mechanism of the sample sectioning device.For example, sample sectioning device may include a control panel 2202associated with the housing (e.g., mounted to housing 102), whichincludes an indicator light 2204 (e.g., an LED) to indicate the handwheel is locked, an indicator light 2206 (e.g., an LED) to indicate thelight source 116 (behind the specimen block) is on. In addition, thecontrol panel 2202 may also include indicators 2208 to indicate thecolor, intensity, wavelength, etc. of the light source 116 as previouslydiscussed. For example, indicator 2208A may indicate a light color,indicator 2208B may indicate a light intensity, indicator 2208C mayindicate a light wavelength, and indicator 2208D may indicate the amountof time a light has been operating, or a status of a light (e.g., alight is burnt out and needs to be replaced). In other embodiments, eachof indicators 2208A-2208D may correspond to, for example, each LEDwithin the light source 116 and indicate a characteristic (e.g., color,intensity, brightness, wavelength or the like) of that specific LED. Forexample, indicator 2208A may indicate a characteristic of a red LED,indicator 2208B may indicate a characteristic of a blue LED, indicator2208C may indicate a characteristic of a green LED, and indicator 2208Dmay indicate a characteristic of a white LED. In other embodiments,indicators 2208A-2208D may be touch sensitive controllers, buttons, orswitches, that can receive user input to control differentcharacteristics of the light source 116. In addition, it is contemplatedthat although the indicator light 2206 is described as a light sourcedifferent than light source 116, in some embodiment, the indicator light2206 may be the light source 116 previously discussed in reference toFIG. 1.

In addition, although a mechanical locking mechanism is discussed inreference to FIG. 21, in some embodiments, the locking mechanism may be,for example, a permanent magnet solenoid, a geared motor or a rotatinghandle that locks by friction or other known manner. In one embodiment,a motor may be used to tighten the chuck at times when the chuck is notbeing adjusted. When the microtome determines to adjust the position ofthe sample by adjusting the chuck, or when a user decides to manuallyadjust the position of the tissue sample by adjusting the chuck, a motormay be signaled to loosen the chuck to allow the chuck to be adjusted.At other times, when the position of the chuck is not being adjusted, amotor may be signaled to maintain the chuck in a tightened or lockedconfiguration so that the position of the chuck and/or the position of asample held by the chuck do not change unintentionally.

It should be understood that in some embodiments, sample holder may beany sample holder capable of realigning an orientation of a surface of asample so that it is parallel or more parallel with a cutting memberand/or a cutting plane. For example, in some embodiments, the sampleholder may be part of a multi-axis workpiece chuck or motorized chuckthat is capable of adjusting an orientation of the cutting surface ofthe sample in two dimensions relative to a cutting member and/or cuttingplane. Examples of suitable multi-axis workpiece chucks are described inU.S. Pat. No. 7,168,694, entitled “MULTI-AXIS WORKPIECE CHUCK,” by XuanS. Bui et al., filed on Jan. 22, 2004, and assigned to the assignee ofthe present application. In one embodiment, the multi-axis chuck mayhave a mounting assembly that retains a workpiece, such as a sample, ina substantially fixed orientation with respect to the chuck. The chuckmay be rotated manually by an operator using a controller that is incommunication with one or more motors, or the microtome may autonomouslyrotate the chuck. One or more sensors may be used to sense a position ofthe chuck. According to one embodiment, each axis may have three sensorsthat detect a middle nominal position and end positions of the chuck. Auser or the microtome may control movement of the chuck by signaling themotor to rotate the chuck to the desired position. The sensors may beused to determine whether the desired position has been reached. In oneembodiment, the chuck may include first and second portions that arerotatable about at least two orthogonal axes. The first portion mayrotate about a first axis and independently of the second portion.Rotation of the second portion about a second axis may cause the firstportion to rotate about the second axis also. This may allow the chuckto be rotatable in multiple dimensions.

In some embodiments, a sample cutting or sectioning cycle may include:(1) moving a sample block in a forward horizontal direction toward thecutting plane a predetermined distance related to the desired slicethickness; (2) moving the sample block in a vertical direction (forexample downward) toward the cutting member to obtain a slice; (3)moving the sample block in a backward or opposite horizontal directionaway from the cutting plane and/or cutting member a predetermineddistance; and (4) moving sample block in an opposite vertical direction(for example upward) away from the cutting member. Retracting or movingthe sample block in a backward horizontal direction away from thecutting member helps to avoid the sample block contacting the cuttingmember during (4) when moving sample block in the opposite verticaldirection (for example upward) away from the cutting member.Representatively, the distance sample block is retracted may correspondto a thickness of the sliced sample. Alternatively, it is contemplatedthat in some embodiments, the retraction step may be omitted. Theslicing cycle may be repeated until a desired number of slices areobtained.

In some embodiments, the microtome may be capable of using differentspeeds of movement of a sample for different portions of a sectioningcycle. For example, in some embodiments, a relatively faster speed ofmovement of the feed drive system and/or a sample may be used during oneor more non-sectioning portions of a sectioning cycle (e.g., wherecutting or sectioning of a sample is not performed), whereas arelatively slower speed of movement of the feed drive system and/or asample may be used during a sectioning portion of the sectioning cycle(e.g., where cutting or sectioning of the sample is performed). Using arelatively slower speed of movement of the feed drive system and/orsample during cutting or sectioning of the sample tends to providehigher quality sections and/or more consistent sections, whereasperforming one or more other non-sectioning portions of the sectioningcycle more rapidly may help to improve the overall speed of thesectioning cycle and/or may allow more sections to be produced in agiven amount of time. As such, the speed of movement of a feed drivesystem and/or a sample may vary throughout a sectioning cycle. Forexample, a user may control or program a sectioning cycle so thatmovement of sample block or sample in a vertical direction (for exampledownward) toward the cutting member to obtain a slice (e.g., operation(2) in the paragraph above) is performed more slowly than one or moreother portions of the sectioning cycle (e.g., operations (1), (3), (4),or a combination thereof, in the paragraph above).

In some embodiments, the microtome may include logic to control anoperation of the light source associated with the sample holder. Forexample, in some embodiments, the microtome may include logic to allow aconfigurable or programmable brightness or color selection to beconfigured or programmed. By way of example, the brightness or color maybe selected based upon a color or other characteristic of the sample. Inone example embodiment, the microtome may be operable to allow anoperator to specify or indicate the type of sample, characteristic ofthe sample (e.g., color) or characteristic of the embedding medium. Themicrotome may include logic which is programmed to, based on thisinformation, select a brightness and/or color of the light to be outputwhich has been determined to allow for a desired level of contrastbetween, for example, the tissue or tissue characteristics and theembedding medium (e.g., paraffin). In other embodiments, the brightnessor color output from the light source may be manually selected by theuser.

In some embodiments, the microtome may include logic to allow aconfigurable or programmable sectioning portion of a sectioning cycle tobe specified over which relatively slower speed of movement of the feeddrive system and/or a sample are to be used. For example, in someembodiments, the microtome may include logic to allow a configurable orprogrammable sectioning length to be configured or programmed. By way ofexample, the length may be selected from among a plurality ofpredetermined lengths corresponding to different types of cassetteshaving different dimensions. Different types of cassettes have differentsectioning lengths over which sectioning is performed. As one example,7019 Paraform® brand Biopsy 13 mm×13 mm Cassettes, and 7020 Paraform®brand Biopsy 26 mm×19 mm Cassettes, which are commercially availablefrom Sakura Finetek USA, Inc., of Torrance, Calif., have differentsectioning lengths. In one example embodiment, the microtome may beoperable to allow an operator to specify or indicate a sectioninglength. The specification or indication of the sectioning length may bedone in different ways, such as, for example, by specifying a length,selecting a length from among a plurality of predetermined lengths,specifying a type of cassette, selecting a type of cassette from among aplurality of different types of cassettes, etc. For example, when a useris ready to product sections from a particular type of cassette, theuser may make a selection of the particular type of cassette using acontrol device, and the microtome may already be preprogrammed with apredetermined sectioning length corresponding to that particular type ofcassette. During sectioning, the microtome may use a relatively slowerspeed of movement of the feed drive system and/or the sample over thespecified sectioning length and may use relatively faster speeds ofmovement over one or more or substantially all other portions of thesectioning cycle. For example, immediately or just before andimmediately or just after the cutting of the sample over the specifiedsectioning length the relatively faster speeds may be used.

In some embodiments, a microtome may include logic to initiallyautonomously remove a given or predetermined portion of a sample. Forexample, the portion may include a given or predetermined thickness ofparaffin, embedding material, cassette material, or other non-tissuematerial overlying or concealing the actual tissue material from which asection is desired to be taken (e.g., disposed between a cutting surfaceof the tissue material and the foremost external surface of the samplewhich would contact a sensing plate). By way of example, a sample mayinclude a piece of tissue placed on a bottom of a cassette and thecassette and the tissue sample embedded in a block of embeddingmaterial. In the case of various cassettes manufactured by SakuraFinetek USA, Inc., of Torrance, Calif., the cassettes may include aParaform® brand cassette material that has sectioning characteristicssimilar to that of paraffin and sectioning may be performed through theParaform® brand cassette material of the cassette bottom.

In some embodiments, a microtome may include logic to initiallyautonomously remove a given or predetermined portion of a sample, forexample, a portion of paraffin, embedding material, cassette material,or other non-tissue material overlying or concealing an actual tissuematerial desired to be sectioned. For example, the microtome mayautonomously remove a bottom of a cassette in order to expose or provideaccess to the actual tissue material of the sample. Representatively, inthe case of certain cassettes, depending upon the thickness of thematerial making up the bottom of the cassette and the thickness of thesections, the microtome may autonomously make a plurality (e.g., fromaround two to about twenty, often from about five to about fifteen) ofsections to remove a predetermined thickness of the bottom of thecassette. The thickness of the bottom of the cassette may be known bythe microtome or predetermined. For example, a user may specify thethickness directly, or select a type of cassette from among severaldifferent types that each has a preprogrammed or otherwise knowncassette bottom thickness. In some cases, the operator may control themicrotome to perform the automated process, for example, with a userinput device (e.g., a trim button) on a control device or otherwiseselecting a trim operation. Advantageously, allowing the microtome toautonomously remove the portion of the sample (e.g., the bottom of thecassette) may relive the operator from having to do so and/or may tendto speed up the removal of the portion of the sample (e.g., the bottomof the cassette). Then, once the actual tissue of the sample is exposed,a sectioning cycle to obtain slices or sections of the tissue may becommenced (e.g., the operator may press a section button or otherwisecause the microtome to take a section from the now exposed cuttingsurface of the tissue sample.

It should also be appreciated that reference throughout thisspecification to “one embodiment”, “an embodiment”, or “one or moreembodiments”, for example, means that a particular feature may beincluded in the practice of the invention. Similarly, it should beappreciated that in the description various features are sometimesgrouped together in a single embodiment, Figure, or description thereoffor the purpose of streamlining the disclosure and aiding in theunderstanding of various inventive aspects. This method of disclosure,however, is not to be interpreted as reflecting an intention that theinvention requires more features than are expressly recited in eachclaim. Rather, as the following claims reflect, inventive aspects maylie in less than all features of a single disclosed embodiment. Thus,the claims following the Detailed Description are hereby expresslyincorporated into this Detailed Description, with each claim standing onits own as a separate embodiment.

In the foregoing specification, the invention has been described withreference to specific embodiments thereof. It will, however, be evidentthat various modifications and changes can be made thereto withoutdeparting from the broader spirit and scope of the invention as setforth in the appended claims. The specification and drawings are,accordingly, to be regarded in an illustrative rather than a restrictivesense.

In the description above, for the purposes of explanation, numerousspecific details have been set forth in order to provide a thoroughunderstanding of the embodiments of the invention. It will be apparenthowever, to one skilled in the art, that one or more other embodimentsmay be practiced without some of these specific details. The particularembodiments described are not provided to limit the invention but toillustrate it. The scope of the invention is not to be determined by thespecific examples provided above but only by the claims below. In otherinstances, well-known circuits, structures, devices, and operations havebeen shown in block diagram form or without detail in order to avoidobscuring the understanding of the description.

It will also be appreciated, by one skilled in the art, thatmodifications may be made to the embodiments disclosed herein, such as,for example, to the sizes, shapes, configurations, couplings, forms,functions, materials, and manner of operation, and assembly and use, ofthe components of the embodiments. All equivalent relationships to thoseillustrated in the drawings and described in the specification areencompassed within embodiments of the invention. Further, whereconsidered appropriate, reference numerals or terminal portions ofreference numerals have been repeated among the figures to indicatecorresponding or analogous elements, which may optionally have similarcharacteristics.

Various operations and methods have been described. Some of the methodshave been described in a basic form, but operations may optionally beadded to and/or removed from the methods. In addition, while aparticular order of the operations according to example embodiments hasbeen described, it is to be understood that that particular order isexemplary. Alternate embodiments may optionally perform the operationsin different order, combine certain operations, overlap certainoperations, etc. Many modifications and adaptations may be made to themethods and are contemplated.

One or more embodiments include an article of manufacture (e.g., acomputer program product) that includes a machine-accessible and/ormachine-readable medium. The medium may include, a mechanism thatprovides (e.g., stores) information in a form that is accessible and/orreadable by the machine. The machine-accessible and/or machine-readablemedium may provide, or have stored thereon, a sequence of instructionsand/or data structures that if executed by a machine causes or resultsin the machine performing, and/or causes the machine to perform, one ormore or a portion of the operations or methods disclosed herein. In oneembodiment, the machine-readable medium may include a tangiblenon-transitory machine-readable storage media. For example, the tangiblenon-transitory machine-readable storage media may include a floppydiskette, an optical storage medium, an optical disk, a CD-ROM, amagnetic disk, a magneto-optical disk, a read only memory (ROM), aprogrammable ROM (PROM), an erasable-and-programmable ROM (EPROM), anelectrically-erasable-and-programmable ROM (EEPROM), a random accessmemory (RAM), a static-RAM (SRAM), a dynamic-RAM (DRAM), a Flash memory,a phase-change memory, or a combinations thereof. The tangible mediummay include one or more solid or tangible physical materials, such as,for example, a semiconductor material, a phase change material, amagnetic material, etc.

It should also be appreciated that reference throughout thisspecification to “one embodiment”, “an embodiment”, or “one or moreembodiments”, for example, means that a particular feature may beincluded in the practice of the invention. Similarly, it should beappreciated that in the description various features are sometimesgrouped together in a single embodiment, Figure, or description thereoffor the purpose of streamlining the disclosure and aiding in theunderstanding of various inventive aspects. This method of disclosure,however, is not to be interpreted as reflecting an intention that theinvention requires more features than are expressly recited in eachclaim. Rather, as the following claims reflect, inventive aspects maylie in less than all features of a single disclosed embodiment. Thus,the claims following the Detailed Description are hereby expresslyincorporated into this Detailed Description, with each claim standing onits own as a separate embodiment of the invention.

What is claimed is:
 1. A sample sectioning device comprising: a housinghaving a base member; a cutting mechanism positioned on the base memberand operable to cut sections from a sample; a sample holder dimensionedto hold a sample and operable to move with respect to the cuttingmechanism during a cutting operation; and a waste removal assemblypositioned below the cutting mechanism and the sample holder, the wasteremoval assembly having a first member and a second member that aredimensioned to remove waste produced during the cutting operation. 2.The sample sectioning device of claim 1 wherein the first member and thesecond member are each movably connected to the base member and operableto move between a first position in which they are at a first angle withrespect to the base member and a second position in which they are at asecond angle with respect to the base member, wherein the second angleis greater than the first angle.
 3. The sample sectioning device ofclaim 1 wherein the first member and the second member are operable tomove with respect to the base member between a first angle of inclineand a second angle of incline, wherein the second angle of incline isapproximately 90 degrees and is greater than the first angle of incline.4. The sample sectioning device of claim 1 wherein the cutting mechanismis operable to slide with respect to the base member, and whereinsliding of the cutting mechanism causes the first member and the secondmember to move with respect to one another.
 5. The sample sectioningdevice of claim 1 wherein the first member and the second member form apitched surface below the cutting mechanism and the sample holder. 6.The sample sectioning device of claim 1 wherein the first member and thesecond member are fixed with respect to one another.
 7. The samplesectioning device of claim 1 further comprising: a temperaturecontrolling member coupled to the first member or the second member tocontrol a temperature thereof.
 8. A waste removal assembly for a samplesectioning device comprising: a first inclined member coupled to amicrotome housing; a second inclined member coupled to a microtomehousing; and an actuator movably coupled to the first inclined memberand the second inclined member, wherein the actuator is operable tocause a slope of one of the first inclined member or the second inclinedmember to change.
 9. The waste removal assembly of claim 8 wherein thefirst inclined member and the second inclined member comprise metalplates.
 10. The waste removal assembly of claim 8 wherein one of thefirst inclined member or the second inclined member comprises a platehaving an edge that is coupled to the sample sectioning device by ahinge.
 11. The waste removal assembly of claim 8 wherein the slope ofthe first inclined member or the second inclined member is a firstslope, and the actuator causes the first inclined member or the secondinclined member to change to a second slope, wherein the second slope isgreater than the first slope.
 12. The waste removal assembly of claim 8wherein the actuator causes the slope of one of the first inclinedmember or the second inclined member to change within a range of ninetydegrees with respect to horizontal.
 13. The waste removal assembly ofclaim 8 wherein the actuator comprises a cutting mechanism of the samplesectioning device, and wherein a sliding of the cutting mechanism causesthe slope of one of the first inclined member or the second inclinedmember to change.
 14. The waste removal assembly of claim 8 wherein theactuator comprises an actuating member and a protrusion, wherein theactuating member slides the protrusion under the first inclined memberand the second inclined member to change the slope.
 15. The wasteremoval assembly of claim 8 wherein the actuator is manually operated bya user.
 16. The waste removal assembly of claim 8 the actuator isautomated.
 17. The waste removal assembly of claim 8 further comprising:a thermoelectric cooler (TEC) coupled to the first member or the secondmember to control a temperature thereof.